This application is for continued support (years 16-20) of research on herpes simplex virus and on cells productively infected with this virus. The application lists 3 projects that concern the structural and functional organization of the viral genome. The aim of the first project is to delineate the organization of viral genes in transcriptional units. We propose to delineate on the physical map of HSV DNA the 5', 3' and intervening sequences of viral mRNA made early in infection (alpha RNA) and of mRNA specifying structural polypeptides late in infection (gamma RNA). The aim of the second project is to elucidate the function of a gene which appears to control the expression of all early functions. The project centers on the properties of a ts mutant which does not shut off the host and does not specify any proteins at the non-permissive temperatures. The aim of the third project is to test specific aspects of the model for replication of HSV-DNA. The project entails transinfection of cells with DNA whose termini have been altered by addition of viral sequences and circularization.